Bioresorbable (also called biodegradable or bioabsorbable) metals are metals or their alloys that degrade safely within the body.[1] The primary metals in this category are magnesium-based[2][3] and iron-based alloys,[4] although recently zinc has also been investigated[5].[6] Currently, the primary uses of bioresorbable metals are as stents for blood vessels (for example bioresorbable stents) and other internal ducts.

Background

Although bioabsorbable polymers and other materials have come into widespread use in recent years, degradable metals have not yet had the same success in the medical industry.

Driving force for development

The driving force behind the development of bioresorbable metals is primarily due to their ability to provide metal-like mechanical properties while degrading safely in the body.[1] This is especially relevant in orthopaedic applications, where although many surgeries only require implants to provide temporary support (allowing the surrounding tissue to heal), the majority of current bio-metals are permanent (e.g. stainless steel, titanium). Degradation of the implant means that intervention or secondary surgery will not be necessary to remove the material at the end of its functional life, providing significant savings in both cost and time for the patient and health care system. In addition, the corrosion products of current bio-metals (which will still corrode in the body to some degree) can generally not be considered biocompatible.

Potential applications

There are a number of applications for biodegradable metals, including cardiovascular implants (i.e. stents) and orthopedics. It is in this latter category where these materials offer the greatest potential. Bioresorbable metals are able to withstand loads that would destroy any currently available polymers, and offer much greater plasticity than bioceramics, which are brittle and prone to fracture. A well-designed implant could provide the exact mechanical support needed for different areas (through alloying and metal working), and load would be transferred to the surrounding tissue over time, letting it heal and reducing the effects of stress shielding.[7] A summary of the primary benefits and drawbacks of magnesium biomaterials has been provided by Kirkland.[2]

Considerations and issues facing bioresorbable metal development

Changing shape over time

It is the same advantage that bioresorbable metals possess over non-degradable current materials, their biodegradability, that poses the greatest challenges to their development and wider use. The degradable nature of any implant means that their shape and thus mechanical properties will change through its lifetime. This means that lifecycle analysis must be performed on any implant, especially one designed for orthopedic applications where failure could result in death.

Lack of standards

Current standards for corrosion of metals have been found to not apply well to bioresorbable metals during in vitro testing.[8] This is a significant problem as the majority of tests performed in the research community are a mix of other standards from both the biomedical and the engineering (e.g. corrosion) communities, often making comparison between results difficult.

Corrosion Product Toxicity

Even though all elements in a bioresorbable metal may themselves be considered biocompatible, the morphology and elemental makeup (or combination of elements) of the degradation products may cause adverse reactions in the body. In addition, the rapid evolution of hydrogen gas that is concomitant with Mg-alloy degradation may cause addition problems in vivo.[9] It is therefore crucial to intricately understand the corrosion of each implant and the products that are release, in light of their toxicity and the likelihood of inflammation. The majority of studies in the literature have focused on elements that are known to be biocompatible or abundant in the body, such as calcium[10][11] and zinc.[12]

Potential bioresorbable metal candidates

Although all metals will degrade and eventually disappear inside the body through the processes of corrosion and wear, true bioresorbable metals must have an appreciable degradation rate to allow the implant to be absorbed in a practical amount of time in reference to their application. Also, any degradation product would have to be safely metabolized or excreted by the body to avoid toxicity and inflammation.

Magnesium

Perhaps the most widely investigated material in this category, magnesium was originally investigated as a potential biomaterial in 1878 when it was used by physician Edward C. Huse in wire form as a ligature to stop bleeding.[13] Development continued into the 1920s, after which Mg-based biomaterials fell out of general investigation due to their poor performance (likely due to impurities in the alloys drastically increasing corrosion). It was not until the late 1990s that interest started to pick up again, Mg has a density close to that of bone and is absorbed by the body .Mg is of interest for orthopedic applications due to its relatively low cost, high specific strength, and near-bone elastic modulus, which provides stress shielding and allows uniform distribution of tissue stress [14][15]

Currently, most research on Mg is focused on reducing and controlling the rate of degradation, with many alloys corroding too rapidly (in vitro) for any practical application.[7][16]

Iron

The majority of iron-based alloy research has been focused on cardiovascular applications, such as stents.[17] However this area receives much less interest in the research community than Mg-based alloys.

Zinc

To date little work has been published on the use of a primarily zinc-based biomaterial, with corrosion rates found to be very low and zinc within a tolerable toxicity range [6][7].Furthermore, Pure Zn has poor mechanical behavior, with a tensile strength of around 100–150 MPa and an elongation of 0.3–2%, which is far from reaching the strength required as an orthopedic implant material (tensile strength is more than 300 MPa, elongation more than 15%). Alloy and composite fabrication have proven to be excellent ways to improve the mechanical performance of Zn.[18]

Biodegradable bulk metallic glasses

Although strictly speaking a side-category, a related, relatively new area of interest has been the investigation of bioabsorbable metallic glass, with a group at UNSW currently investigating these novel materials.[19]

References

  1. 1 2 Kirkland, N; Birbilis N (2013). Magnesium Biomaterials: Design, Testing and Best Practice. New York: Springer. ISBN 978-3-319-02123-2. Retrieved 26 November 2013.
  2. 1 2 Kirkland, N. T. (2012). "Magnesium biomaterials: Past, present and future". Corrosion Engineering, Science and Technology. 47 (5): 322–328. doi:10.1179/1743278212Y.0000000034. hdl:10069/29852. S2CID 135864605.
  3. ↑ Saberi A, Bakhsheshi-Rad HR, Karamian E, Kasiri-Asgarani M, Ghomi H. Magnesium-graphene nano-platelet composites: Corrosion behavior, mechanical and biological properties. Journal of Alloys and Compounds. 2020 Apr 25;821:153379.https://doi.org/10.1016/j.jallcom.2019.153379
  4. ↑ Peuster, M.; Wohlsein, P.; Brügmann, M.; Ehlerding, M.; Seidler, K.; Fink, C.; Brauer, H.; Fischer, A.; Hausdorf, G. (2001). "A novel approach to temporary stenting: Degradable cardiovascular stents produced from corrodible metal---results 6-18 months after implantation into New Zealand white rabbits". Heart. 86 (5): 563–569. doi:10.1136/heart.86.5.563. PMC 1729971. PMID 11602554.
  5. ↑ Kong, L.; Heydari, Z.; Lami, G.H.; Saberi, A.; Baltatu, M.S.; Vizureanu, P. A Comprehensive Review of the Current Research Status of Biodegradable Zinc Alloys and Composites for Biomedical Applications. Materials 2023, 16, 4797. https://doi.org/10.3390/ma16134797 https://pubmed.ncbi.nlm.nih.gov/37445111/
  6. 1 2 Vojtěch, D.; Kubásek, J.; Šerák, J.; Novák, P. (2011). "Mechanical and corrosion properties of newly developed biodegradable Zn-based alloys for bone fixation". Acta Biomaterialia. 7 (9): 3515–3522. doi:10.1016/j.actbio.2011.05.008. PMID 21621017.
  7. 1 2 3 Ibrahim, H.; Esfahani, S. N.; Poorganji, B.; Dean, D.; Elahinia, M. (January 2017). "Resorbable bone fixation alloys, forming, and post-fabrication treatments". Materials Science and Engineering: C. 70 (1): 870–888. doi:10.1016/j.msec.2016.09.069. PMID 27770965.
  8. ↑ Witte, F.; Fischer, J.; Nellesen, J.; Crostack, H. A.; Kaese, V.; Pisch, A.; Beckmann, F.; Windhagen, H. (2006). "In vitro and in vivo corrosion measurements of magnesium alloys". Biomaterials. 27 (7): 1013–1018. doi:10.1016/j.biomaterials.2005.07.037. PMID 16122786.
  9. ↑ Kuhlmann, J.; Bartsch, I.; Willbold, E.; Schuchardt, S.; Holz, O.; Hort, N.; Höche, D.; Heineman, W. R.; Witte, F. (2012). "Fast escape of hydrogen from gas cavities around corroding magnesium implants" (PDF). Acta Biomaterialia. 9 (10): 8714–21. doi:10.1016/j.actbio.2012.10.008. PMID 23069319.
  10. ↑ Kirkland, N. T.; Birbilis, N.; Walker, J.; Woodfield, T.; Dias, G. J.; Staiger, M. P. (2010). "In-vitro dissolution of magnesium-calcium binary alloys: Clarifying the unique role of calcium additions in bioresorbable magnesium implant alloys". Journal of Biomedical Materials Research Part B: Applied Biomaterials. 95B (1): 91–100. doi:10.1002/jbm.b.31687. PMID 20725953.
  11. ↑ Cao, J. D.; Martens, P.; Laws, K. J.; Boughton, P.; Ferry, M. (2013). "Quantitativein vitroassessment of Mg65Zn30Ca5degradation and its effect on cell viability". Journal of Biomedical Materials Research Part B: Applied Biomaterials. 101B (1): 43–49. doi:10.1002/jbm.b.32811. PMID 22997106.
  12. ↑ Brar, H. S.; Platt, M. O.; Sarntinoranont, M.; Martin, P. I.; Manuel, M. V. (2009). "Magnesium as a biodegradable and bioabsorbable material for medical implants". JOM. 61 (9): 31. Bibcode:2009JOM....61i..31B. doi:10.1007/s11837-009-0129-0. S2CID 40436409.
  13. ↑ Huse, Edward C. (1878). "A New Ligature?". Chicago Medical Journal and Examiner. 37: 171–172. PMID 37617179.
  14. ↑ Saberi A, Bakhsheshi-Rad HR, Karamian E, Kasiri-Asgarani M, Ghomi H. Magnesium-graphene nano-platelet composites: Corrosion behavior, mechanical and biological properties. Journal of Alloys and Compounds. 2020 Apr 25;821:153379. https://www.sciencedirect.com/science/article/abs/pii/S0925838819346250
  15. ↑ Liu J, Wang X, Saberi A, Heydari Z. The effect of Co-encapsulated GNPs-CNTs nanofillers on mechanical properties, degradation and antibacterial behavior of Mg-based composite. Journal of the Mechanical Behavior of Biomedical Materials. 2023 Feb 1;138:105601.https://www.sciencedirect.com/science/article/abs/pii/S1751616122005069
  16. ↑ Kirkland, N. T.; Lespagnol, J.; Birbilis, N.; Staiger, M. P. (2010). "A survey of bio-corrosion rates of magnesium alloys". Corrosion Science. 52 (2): 287. doi:10.1016/j.corsci.2009.09.033.
  17. ↑ Moravej, M.; Mantovani, D. (2011). "Biodegradable Metals for Cardiovascular Stent Application: Interests and New Opportunities". International Journal of Molecular Sciences. 12 (7): 4250–4270. doi:10.3390/ijms12074250. PMC 3155349. PMID 21845076.
  18. ↑ Kong L, Heydari Z, Lami GH, Saberi A, Baltatu MS, Vizureanu P. A comprehensive review of the current research status of biodegradable zinc alloys and composites for biomedical applications. Materials. 2023 Jul 3;16(13):4797.https://www.mdpi.com/1996-1944/16/13/4797
  19. ↑ University of New South Wales (2010). "BMGs for Electronic, Biomedical and Aerospace Applications". Archived from the original on 5 January 2013. Retrieved 7 January 2013.
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